FDA Grants FTD to WTX-124 in Advanced Pretreated Cutaneous Melanoma

The FDA has granted fast track designation to WTX-124, a conditionally activated interleukin 2 (IL-2) INDUKINE™ therapy, for the potential treatment of patients with locally advanced or metastatic cutaneous melanoma following standard-of-care immunotherapy, according to a press release from the developer, Werewolf Therapeutics.¹

INDUKINE molecules, which are systemically administered in inactive forms and selectively activate to deliver cytokines to the tumor microenvironment and elicit an anti-tumor immune response, were designed by the developer’s PREDATOR® program.²

The FDA’s designation came after WTX-124 achieved clinically meaningful anti-tumor activity with a tolerable safety profile in patients with cutaneous melanoma who received prior treatment with immune checkpoint inhibitors. WTX-124 was evaluated as monotherapy and in combination with pembrolizumab (Keytruda) in multiple advanced solid tumors in an open-label, multicenter phase 1/1b trial (NCT05479812).

“At Werewolf, we are focusing on efforts to address the high unmet need of [patients with cancer], and we believe there is significant opportunity with WTX-124 for the potential treatment of advanced cancers,” stated Daniel J. Hicklin, PhD, president and chief executive officer of Werewolf, in the press release.¹ “We are encouraged by this fast track designation as an important milestone for the WTX-124 program and because it underscores the urgent need for patients with relapsed/refractory melanoma where treatment options are limited. In the fourth quarter, we anticipate sharing preliminary data from the ongoing WTX-124 phase 1/1b clinical trial, including in patients with cutaneous melanoma, and engaging with the FDA regarding the potential registration strategy for this agent.”

The phase 1/1b trial consisted of 2 parts: part 1, the dose-escalation phase, where patients received WTX-124 as monotherapy or in combination with pembrolizumab in escalating doses; and part 2, the dose-expansion part, where 6 arms of patients with advanced cutaneous melanoma or advanced renal cell carcinoma received either monotherapy or combination therapy.³

The trial had an estimated enrollment of 150 patients, began on May 20, 2022, and has an estimated study completion date of July 31, 2026.

Eligible patients were 18 years or older and had histological or cytological confirmation of a solid tumor indication that had a checkpoint inhibitor indicated for all parts of the study, an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 criteria, and adequate organ function. In the monotherapy and combination dose-escalation parts of the trial, patients with relapsed/refractory locally advanced or metastatic solid tumors who were approved for immunotherapy and progressed on standard therapy, who demonstrated no proven benefit with standard therapy, were enrolled.

In the monotherapy dose-expansion part of the trial, arm B enrolled patients with relapsed advanced or metastatic cutaneous malignant melanoma who received no more than 2 prior lines of therapy for BRAF V600 wild-type disease and no more than 3 prior lines of therapy for BRAF V600 mutant melanoma. In the combination dose-expansion part, patients in arm E had cutaneous melanoma and were possibly naïve to all prior therapy for advanced or metastatic disease; they also received no more than 2 prior lines of therapy for BRAF V600 wild-type disease and no more than 3 prior lines of therapy for BRAF V600-mutant melanoma.

Exclusion criteria included history of another active malignancy within the 2 previous years, except those that were not related to the current cancer being treated, considered cured, and presented a low risk of recurrence; receipt of prior IL-2–directed therapy; history of allogeneic tissue and solid organ transplant; significant cardiovascular disease; and active autoimmune disease that required systemic treatment in the past 2 years.

The primary end points of the trial included the incidence of dose-limiting toxicities with monotherapy and combination therapy and the incidence of treatment-emergent adverse events. In the dose-expansion part, they included the investigator-assessed objective response rate per RECIST v1.1 criteria.

References

1. Werewolf Therapeutics receives fast track designation from the U.S. FDA for WTX-124, an investigational therapy for the treatment of cancer. News release. Werewolf Therapeutics. October 8, 2025. Accessed October 9, 2025. https://shorturl.at/JJ0VB
2. Our science. Transforming cancer treatment through innovation. Werewolf Therapeutics. Accessed October 9, 2025. https://shorturl.at/Jprbf
3. Dose escalation and expansion study of WTX-124 as monotherapy and in combination with pembrolizumab (Pembro) in patients with selected advanced or metastatic solid tumors. ClinicalTrials.gov. Updated July 28, 2025. Accessed October 9, 2025. https://shorturl.at/c1b87